To design a clinically translatable nanomedicine for photodynamic theranostics, the ingredients should be carefully considered. A high content of nanocarriers may cause extra toxicity in metabolism, ...and multiple theranostic agents would complicate the preparation process. These issues would be of less concern if the nanocarrier itself has most of the theranostic functions. In this work, a poly(ethylene glycol)‐boron dipyrromethene amphiphile (PEG‐F54‐BODIPY) with 54 fluorine‐19 (19F) is synthesized and employed to emulsify perfluorohexane (PFH) into a theranostic nanoemulsion (PFH@PEG‐F54‐BODIPY). The as‐prepared PFH@PEG‐F54‐BODIPY can perform architecture‐dependent fluorescence/photoacoustic/19F magnetic resonance multimodal imaging, providing more information about the in vivo structure evolution of nanomedicine. Importantly, this nanoemulsion significantly enhances the therapeutic effect of BODIPY through both the high oxygen dissolving capability and less self‐quenching of BODIPY molecules. More interestingly, PFH@PEG‐F54‐BODIPY shows high level of tumor accumulation and long tumor retention time, allowing a repeated light irradiation after a single‐dose intravenous injection. The “all‐in‐one” photodynamic theranostic nanoemulsion has simple composition, remarkable theranostic efficacy, and novel treatment pattern, and thus presents an intriguing avenue to developing clinically translatable theranostic agents.
A versatile theranostic nanoemulsion is synthesized by using a PEG‐F54‐BODIPY amphiphile as the emulsifier. Taking advantage of the delicate interactions of the nanocarrier and interior perfluorocarbon, both architecture‐dependent trimodal imaging and highly efficient photodynamic therapy are achieved.
Nitroreductase (NTR) is an important biomarker widely used to evaluate the degree of tumor hypoxia. Although a few optical methods have been reported for detecting nitroreductase at low concentration ...ranges, an effective strategy for nitroreductase monitoring in vivo without limits to the imaging depth is still lacking. Herein, a novel dual‐mode NIR fluorescence and 19F MRI agent, FCy7‐NO2, is proposed for imaging tumor hypoxia. We show that FCy7‐NO2 serves as not only a rapid NIR fluorescence enhanced probe for monitoring and bioimaging of nitroreductase in tumors, but also a novel 19F MR chemical shift‐sensitive contrast agent for selectively detecting nitroreductase catalyzed reduction. Notably, integrating two complementary imaging technologies into FCy7‐NO2 enables sensitive detection of nitroreductase in a broad concentration range without tissue‐depth limit. In general, this agent has a remarkable response to nitroreductase, which provides a promising method for understanding tumor evolution and its physiological role in the hypoxic microenvironment.
We report a bimodal probe to detect hypoxic tumors by both fluorescence and chemical shift dependent 19F NMR imaging under the catalysis of nitroreductase. Specifically, the concentration of nitroreductase can be detected in a broad range by fluorescence and 19F NMR, which is ≤1.5 μg mL−1 and 10–50 μg mL−1, respectively.
A metal‐free direct trifluoromethylthiolation of sulfonium ylides with an electrophilic trifluoromethylthiolating reagent has been established, in which sulfonium salt or α‐bromoacetic ester is ...employed as sulfonium ylide precursors. This trifluoromethylthiolation enables the straightforward construction of SCF3‐substituted sulfonium ylides from a wide range of substrates, including ketones, esters, and even PEGylated substrates. Moreover, the application of this approach in large‐scale preparation and the fluorescence and fluorine‐19 magnetic resonance imaging capabilities of the product are also explored.
A convenient strategy was developed for highly branched and multifunctionalized peptidic monodisperse polyethylene glycol "brushes", which exhibit remarkable physicochemical and biological properties ...and potential as versatile biomaterials.
A macrocyclic sulfate (MCS)‐based approach to monodisperse poly(ethylene glycols) (M‐PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) ...(OEGs) provides MCS (up to a 62‐membered macrocycle) as versatile precursors for a range of monofunctionalized M‐PEGs. Through iterative nucleophilic ring‐opening reactions of MCS without performing group protection and activation, a series of M‐PEGs, including the unprecedented 64‐mer (2850 Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of M‐PEGs.
Macrocycles make synthesis easier: Convenient macrocyclization of the OEGs provides versatile macrocyclic sulfates. These compounds are cornerstones for both monofunctionalization of OEGs and highly efficient synthesis of monodisperse PEGs and derivatives, including an unprecedented 64‐mer.
The immune checkpoint blockade strategy has improved the survival rate of late‐stage lung cancer patients. However, the low immune response rate limits the immunotherapy efficiency. Here, we report a ...ROS‐responsive Fe3O4‐based nanoparticle that undergoes charge reversal and disassembly in the tumor microenvironment, enhancing the uptake of Fe3O4 by tumor cells and triggering a more severe ferroptosis. In the tumor microenvironment, the nanoparticle rapidly disassembles and releases the loaded GOx and the immune‐activating peptide Tuftsin under overexpressed H2O2. GOx can consume the glucose of tumor cells and generate more H2O2, promoting the disassembly of the nanoparticle and drug release, thereby enhancing the therapeutic effect of ferroptosis. Combined with Tuftsin, it can more effectively reverse the immune‐suppressive microenvironment and promote the recruitment of effector T cells in tumor tissues. Ultimately, in combination with α‐PD‐L1, there is significant inhibition of the growth of lung metastases. Additionally, the hyperpolarized 129Xe method has been used to evaluate the Fe3O4 nanoparticle‐mediated immunotherapy, where the ventilation defects in lung metastases have been significantly improved with complete lung structure and function recovered. The ferroptosis‐enhanced immunotherapy combined with non‐radiation evaluation methodology paves a new way for designing novel theranostic agents for cancer therapy.
A self‐supplying ROS‐responsive Fe3O4 nanoparticle was designed to enhance the therapeutic efficacy of ferroptosis and immunotherapy by ROS‐mediated size reduction and charge reversion. Moreover, the 129Xe MRI of lung metastases showed significant differences in lung ventilation defects in the treatment and control groups, indicating the great potential of 129Xe MRI for monitoring the immunotherapeutic efficacy of lung metastatic cancer.
Monodisperse polyethylene glycols-modified (M-PEGylated) biomaterials exhibit high structural accuracy, biocompatibility, and fine-tunable physicochemical properties. To develop "smart" drug delivery ...systems in a controllable and convenient manner, a peptidic M-PEG "comb" with fluorinated L-lysine side chains and a fluorescent N-terminal is conveniently prepared as a
F magnetic resonance imaging (
F MRI) and fluorescence dual-imaging traceable and thermo-responsive "add-on" module for liposomal theranostics in cancer therapy. The peptidic M-PEG "comb" has high biocompatibility, thermo-responsivity with a sharp lower critical solution temperature, an aggregation-induced emission fluorescence, and high
F MRI sensitivity. As a highly branched amphiphile, it self-assembles and firmly anchors on the doxorubicin-loaded liposomal nanoparticles, which M-PEGylates the liposomes and facilitates the thermo-responsive drug release and drug tracking with dual-imaging technologies. In a rodent xenograft model of human liver cancer HepG2 cells, the M-PEGylated liposomes exhibit long in vivo half time, low toxicity, high tumor accumulation, "hot spot"
F MRI, and therapeutic efficacy. With accurately programmable chemical structure, fine-tunable physicochemical and biological properties to meet the demands of diagnosis, drug delivery, and therapy, the M-PEG "comb" is promising as a versatile "add-on" module for rapid and convenient formulation of various "smart" theranostics.
An efficient, Pd(OAc)2 catalyzed method for direct olefination of highly electron-deficient perfluoroarenes was developed. The reaction scope includes a series of activated and nonactivated alkenes ...in moderate to high yields with moderate to high regio- and stereoselectivities.
The Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) plays a pivotal role in growth factor and cytokine signaling. Gain-of-function SHP2 mutations are associated with Noonan ...syndrome, various kinds of leukemias, and solid tumors. Thus, there is considerable interest in SHP2 as a potential target for anticancer and antileukemia therapy. We report a salicylic acid based combinatorial library approach aimed at binding both active site and unique nearby subpockets for enhanced affinity and selectivity. Screening of the library led to the identification of a SHP2 inhibitor II-B08 (compound 9) with highly efficacious cellular activity. Compound 9 blocks growth factor stimulated ERK1/2 activation and hematopoietic progenitor proliferation, providing supporting evidence that chemical inhibition of SHP2 may be therapeutically useful for anticancer and antileukemia treatment. X-ray crystallographic analysis of the structure of SHP2 in complex with 9 reveals molecular determinants that can be exploited for the acquisition of more potent and selective SHP2 inhibitors.
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